We are applying for the renewal of our grant, continuously supported by NHLBI for about 47 years. The Aims stem from our initial investigations of enzymes that metabolize peptides such as bradykinin (BK), angiotensins and others. lilhibitors of angiotensin I converting enzyme (kininase II;ACE) are currently used to treat millions of patients with hypertension and various cardiovascular diseases. Although their therapeutic actions were thought to be due solely to blocking the generation of hypertensive angiotensin I and inactivation of hypotensive BK, ACE inhibitors enhance the effect of BK and its ACE-resistant peptide analogues on their receptors (B2, B1) by indirect and direct modes of actions.